Lungs are essential organs for respiration, facilitating gas exchange between the human body and the atmosphere by delivering oxygen from the air into the venous blood and extracting carbon dioxide from the blood at the same air-blood interface. Moreover, lungs play other critical roles in physiology, including rapid modulation of blood pH, thermoregulation, and immunoprotection. Despite the specific function being performed by a lung at any given time, however, from an anatomic standpoint, each lung is attached by its root and pulmonary ligament to the heart and trachea, but is otherwise free in the thoracic cavity. Moreover, with respect to human lungs, human lungs consists of the left and right lungs, with the two lungs being located in the chest on either side of the heart and each having an apex, three surfaces (costal, medial, and diaphragmatic), and three borders (anterior, inferior, and posterior). Each lung is surrounded by a closed pleural cavity formed from a two-layered, membrane structure, namely the outer pleura (parietal pleura) that is attached to the chest wall and the inner pleura (visceral pleura) that covers the lungs and divides the two lungs into five lobes. The left lung has two lobes, the left upper lobe (LUL) and the left lower lobe (LLL), which are separated by an oblique fissure. The right lung, on the other hand, is partitioned into three lobes: the right upper lobe (RUL); the right middle lobe (RML); and the right lower lobe (RLL). The RUL and RML are separated by a horizontal fissure and the RML and RLL are separated by an oblique fissure. Through the separation of the various lung loads by the fissures, the lung lobes are thus allowed to slide against the chest wall and adjacent lobes during respiration, and thereby provide the means to reduce lung parenchymal distortion and avoid regions of high local stress that may otherwise impede lung function.
Typically, lung tissue function depends upon the material properties of the lung parenchyma and the relationships between the lungs, diaphragm, and other parts of the respiratory system. The mechanical properties of lung parenchymal tissue are both elastic and dissipative, as well as being highly nonlinear. Yet, pulmonary diseases and/or injuries can change the tissue material properties of lung parenchyma. For example, pulmonary emphysema, a chronic obstructive pulmonary disease (COPD), is characterized by loss of elasticity (increased compliance) of the lung tissue from destruction of structures supporting the alveoli and destruction of capillaries feeding the alveoli. As another example, idiopathic pulmonary fibrosis (IPF), a classic interstitial lung disease, causes inflammation and fibrosis of tissue in the lungs and, over time, the disease makes the tissue thicker and stiffer (reduced compliance) and subsequently leads to associated mechanical changes within the lung itself.
To date, computed tomography (CT) has been the primary means to efficiently and effectively analyze the changes in lung function associated with pulmonary diseases and injuries. In this regard, CT theory, techniques, and applications have seen continuous development over the years, including advances in X-ray CT, such as transition from fan-beam to cone-beam geometry, from single-row detector to multiple-row detector arrays, and from conventional to spiral CT that permits a larger scanning range in shorter time and with a higher image resolution. More specifically, first generation CT only consisted of a single detector and a sharply collimated X-ray beam, and the attenuation profile was recorded during a translation of both the source and detector, which was followed by a rotation of both the detector and the X-ray tube to generate the projection profile for a different angle. Second generation scanners acquired the data in the same manner, but utilized several detector elements and an X-ray fan beam with less collimation, and a separate translational movement was still part of the acquisition process. In third generation scanners, only a rotation of the curved detector row together with the X-ray tube was carried out. A stationary detector ring with rotating X-ray tube was used in the fourth generation systems, and helical CT was then developed to cover a larger volume of the body in a short time, where the data are acquired as the table position was moved continuously in the scanner. Such a simultaneous motion of the patient bed and rotation of the X-ray source and detectors then resulted in a spiral trajectory of the X-ray transmitted through patient. In all, seven generations of X-ray CT systems have now been developed, with the latest generation being cone-beam CT systems having many detector rows (256 rows are now available) and capable of performing helical scans.
Despite advances in CT imaging, however, respiratory motion often degrades anatomic position reproducibility during imaging. In turn, that degradation then necessitates larger margins to be drawn during certain therapy planning, such as during radiotherapy planning where smaller margins can cause errors during radiation delivery. For instance, radiation therapy is a standard technique for cancer treatment where cancer cells are destroyed by highly energetic ionizing radiation. In particular, in conformal radiation therapy, high-energy radiation beams from several angles are focused precisely onto the tumor and, ideally, these beams overlap exactly in the tumor so that the tumor receives the maximum dose of radiation while the radiation in the surrounding healthy tissue is minimized. Likewise, in intensity-modulated radiation therapy (IMRT) radiation beams are delivered in approximately 300 different segments, focusing the radiation on the tumor and giving radiation therapists the ability to sculpt the edges of a tumor and minimize damage to adjacent healthy tissue. Moreover, in image-guided radiation therapy (IGRT), repeated imaging scans are performed during treatment to identify changes in a tumor's size and location due to treatment and to allow needed adjustments in the position of the patient or the planned radiation doses. In all of these types of radiation therapy, however, large margins around a tumor must typically be drawn as the imaging often prevents precise anatomical mapping of the tumor and healthy tissue.
In this regard, CT scans acquired synchronously with the respiratory signal can be used to reconstruct 4-D CT scans, which can be employed for 4-D treatment planning. This approach explicitly accounts for the respiratory motion and provides an estimate of the intrathoracic tumor motion by acquiring a sequence of 3-D CT image sets over consecutive segments of a breathing cycle. After 4-D CT data acquisition and image reconstruction, a software algorithm can then retrospectively sort the images into multiple temporally coherent volumes.
In most thoracic 4-D CT studies, ten respiratory phases are imaged and these are typically referred to as phases P00, P10, . . . , P90, where phase P00 corresponds to end-inhale and phase P50 corresponds to end-exhale. The full set of images provides a movie of the internal anatomical motion resulting from a sampled respiratory cycle and has found some use for tumor targeting in radiotherapy treatment planning. Nevertheless, registration of such large data sets requires a computationally efficient image registration algorithm. Furthermore, the image acquisition process often renders the resulting thoracic CT images prone to noise, blurring, and image artifacts. Moreover, motion reproducibility assumption with respect to the breathing index and insufficient number of projections per breathing phase for volumetric 3-D reconstruction continue to be frequent limitations of 4-D CT.